| Project/Area Number |
09044280
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research . |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tokai University |
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Principal Investigator |
MIYATA Toshio Tokai University, 総合医学研究所, 講師 (10222332)
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| Co-Investigator(Kenkyū-buntansha) |
VAN Ypersele ルパイン大学, 医学部, 教授
JOHN W. Bayn サウスカロライナ大学, 医学部, 教授
STERN David Columbia University, Professor, 細胞生理学部, 教授
MONNIER Vincent M. Case Western Reserve University, Professor, 病理研究所, 教授
BAYNES John W. University of South Carolina, Professor
C.VAN Ypersele de Striho University of Louvain Medical School, Professor
DE Strihou C ルバイン大学, 医学部, 教授
BAYNES John サウスカロライナ大学, 医学部, 教授
DAIVID Stern コロンビア大学, 細胞生理学部, 教授
C.VAN Yperse ルバイン大学, 医学部, 教授
STERN Daivid コロンビア大学, 細胞性理学部教授, 教授
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Oxidative stress / Carbonyl stress / AGEs / Renal failure / Reduction and oxidation / Diabetes mellitus / Pentosidine |
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| Research Abstract |
Proteins are modified with advanced glycation end products (AGEs) formed by non - enzymatic glycation and oxidation (glycoxidation) reaction. Research on AGEs in human pathology initially focused on diabetes with sustained hyperglycemia. Recent studies, however, demonstrated the increased AGE genesis in normoglycemic uremia and atherosclerosis. Their AGE accumulation cannot be attributed to hyperglycemia. Gathered evidence has suggested that, under oxidative stress, the increased carbonyl compounds, derived from both carbohydrates and lipids, modify proteins by not only glycoxidation reaction but also lipoxidation reaction, leading to formation of not only AGEs but also advanced lipoxidation end products (ALEs). Thus, the pathological lesions might be in a state of carbonyl overload with potentially damaging proteins ("carbonyl stress"). The increased AGEs/ALEs in tissue proteins may betray abroad derangement in non - enzymatic biochemistry involving both carbohydrates and lipids. Immu
… More
nohistochemical studies with specific antibodies to AGEs /ALEs, identified "carbonyl stress" in human atherosclerosis, diabetic nephropathy, uremic dialysis related amyloidosis._Proteins modified with AGEs/ALEs exhibited various biological effects on several types of cells. The carbonyl compounds per se crosslink matrix proteins and alter their structure and function. They further interact with cell surface proteins, transduce the intracellular signaling, and induce cellular responses. These biological activities might account in part for the pathology.
We recently found a novel compound that inhibits the carbonyl stress and AGE/ALE formation. This compound inhibits the intracellular protein - tyrosine phosphorylation in cultured cells exposed to carbonyl compounds. Oral administration of the compound in a rat carotid artery balloon injury model effectively inhibited the neointimal proliferation. These findings suggest the usefulness of carbonyl compound entrapping in the treatment of the diseases. Less
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